(C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6
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| Authors: | Lat, PK; Sen, D |
| Year: | 2018 |
| Journal: | PLoS One 13 Article Link (DOI) PubMed |
| Title: | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
| Abstract: | Massive expansion of a DNA hexanucleotide sequence repeat (C(2)G(4)) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C(2)G(4))(n) DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C(2)G(4))(n) oligonucleotides fold to form a distinctive higher order structure whose most striking feature is an "inverted" circular dichroism spectrum, which is distinguishable from the spectrum of the left handed DNA double-helix, Z-DNA. On the basis of CD spectroscopy, gel mobility as well as chemical protection analysis, we propose that this structure, which we call "iCD-DNA", may be a left-handed Hoogsteen base-paired duplex, an unorthodox G-quadruplex/i-motif composite, or a non-canonical, "braided" DNA triplex. Given that iCD-DNA forms under slightly acidic solution conditions, we do not know at this point in time whether or not it forms within living cells. |
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